Use of acylphosphonates for the synthesis of α-chlorinated carboxylic and α,α′-dichloro dicarboxylic acids and their derivatives

Article abstract of DOI:10.1016/S0040-4020(01)00407-0

α-Chloro acylphosphonates and α,α′-dichloro bisacylphosphonates were prepared in situ by chlorination of acylphosphonates and bisacylphosphonates, respectively, using sulfuryl chloride. Subsequently, they were cleaved to the corresponding α-chlorinated or α,α′-dichlorinated (di)carboxylic acids with a hydrogen peroxide-sodium bicarbonate system. Performing the cleavage with an alcohol or an amine yielded the corresponding α-chlorinated esters and α-chlorinated amides, respectively.

Full text of DOI:10.1016/S0040-4020(01)00407-0

TETRAHEDRON
Pergamon
Tetrahedron 57 *2001) 4793±4800
Use of acylphosphonates for the synthesis of a-chlorinated
carboxylic and a,a0-dichloro dicarboxylic acids
and their derivatives
Christian V. Stevensp and Bart Vanderhoydonck
Faculty of Agricultural and Applied Biological Sciences, Department of Organic Chemistry, Ghent University, Coupure Links 653,
B-9000 Ghent, Belgium
Received 19 January 2001; revised 16 March 2001; accepted 5 April 2001
AbstractÐa-Chloro acylphosphonates and a,a0-dichloro bisacylphosphonates were prepared in situ by chlorination of acylphosphonates
and bisacylphosphonates, respectively, using sulfuryl chloride. Subsequently, they were cleaved to the corresponding a-chlorinated or
a,a0-dichlorinated *di)carboxylic acids with a hydrogen peroxide±sodium bicarbonate system. Performing the cleavage with an alcohol
or an amine yielded the corresponding a-chlorinated esters and a-chlorinated amides, respectively. q 2001 Elsevier Science Ltd. All rights
reserved.
1. Introduction
and adipic acid,15±17 no methods for longer dicarboxylic
acids are described to our knowledge. Recently, our labora-
tory reported a new procedure to synthesize a-chloro
carboxylic acids 3 at room temperature, without a com-
peting chlorination in the aliphatic chain, starting from the
corresponding dimethyl acylphosphonates 1 *Scheme 1).18
The preparation of a-chloro carboxylic acids has been the
subject of numerous industrial studies because of their
importance in several domains, e.g. agrochemistry1,2 and
¯otation chemistry.3 Furthermore, a-chloro carboxylic
acids and a,a0-dichloro dicarboxylic acids have been
reported to stabilize photographical silver halide emul-
sions.4 Several synthetic methods have been described,
however most of them face the problem of free-radical
chlorination in the alkyl chain. In contrast with the a-bromi-
nation in the Hell±Volhard±Zelinsky reaction, the a-chlori-
nation with chlorine gas in the presence of phosphorus is
less selective.5,6 To suppress the radical chlorination, radical
scavengers, e.g. oxygen and 7,7,8,8-tetracyanoquinodi-
methane are extensively used.6±10 Some alternative pro-
cedures have been described, including: chlorination with
thionyl chloride mediated by ultraviolet light;11 chlorination
with N-chlorosuccinimide in thionyl chloride at 908C;5
chlorination with sulfuryl chloride in the presence of
benzoyl peroxide or pyridine at 708C.12 Except for some
procedures for the a,a0-dichlorination of glutaric acid13,14
The convenience of the a-monochlorination, due to the acti-
vating phosphonate function, and the ease of the deprotec-
tion of the acid function, offers a perspective to establish a
more general method for the synthesis of a,a0-dichloro
dicarboxylic acids, a-chloro esters, a-chloro amides,
a,a0-dichloro diesters and a,a0-dichloro diamides. In this
paper, we want to disclose the expansion of this method to
the a-chloro derivatives mentioned and to rediscuss the
mechanism of the reaction which has now been proved
experimentally.
2. Results and discussion
In an earlier report,18 a mechanism was proposed for the
Scheme 1.
Keywords: acylphosphonates; monochlorination; Baeyer±Villiger oxidation.
Corresponding author. Tel.: 132-9-264-6243; fax: 132-9-264-5957; e-mail: chris.stevens@rug.ac.be
p
0040±4020/01/$ - see front matter q 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020*01)00407-0

4794
C. V. Stevens, B. Vanderhoydonck / Tetrahedron 57 .2001) 4793±4800
Scheme 2.
Scheme 3.
hydrolysis of the a-chloro acylphosphonate 2 to the corre-
sponding a-chloro carboxylic acid 3 using hydrogen perox-
ide and sodium bicarbonate *Scheme 2). It was believed that
after an addition±elimination step, the a-chloro peroxy acid
5 was formed. The liberated dimethyl phosphite 6 would
then reduce the peroxy acid resulting in the formation of
the a-chloro carboxylic acid 3.
the signal of 6 *d: 10.77 ppm) is almost directly replaced by
a signal attributable to the formation of dimethyl phosphate
9 *d: 1.00 ppm). Accepting this mechanism, the a-chloro
peroxy acid 5 should be formed because of the lack of
reductants. Asimple test, 19 however, proved that no peroxy
acid was formed as the result of the reaction sequence *see
experimental section). Since the a-chloro carboxylic acid 3
was formed, two alternative reaction mechanisms were
suggested *Scheme 3).
However, the proposed mechanism appears to be improb-
able since the hydrolysis is performed with an excess of
hydrogen peroxide±sodium bicarbonate. Therefore, it
seems more likely that dimethyl phosphite 6 is oxidized
directly by the excess of hydrogen peroxide. The oxidation
of 6 to dimethyl phosphate indeed proceeds very fast as
observed in an experiment following the oxidation of 6
with hydrogen peroxide±sodium bicarbonate by 31P NMR:
Mechanism a, as well as mechanism b, starts with the addi-
tion of the hydrogen peroxide anion to 2. A®rst possibility
*mechanism a) involves a 4-center-mechanism leading to
a-chloro carboxylic acid 8 and dimethyl phosphate 9.
Mechanism b, however, gives rise to the formation of
dimethyl a-chloro acylphosphate 10 as an intermediate
which is subsequently hydrolysed leading to 3 and 11.
Using 31P NMR we were able to prove that mechanism b
is the pathway by which the cleavage of 2 occurs. The 31P
NMR signal of 2 *d: 21.54 ppm) gradually disappeared
when hydrogen peroxide±sodium bicarbonate was added.
Both mechanism a and mechanism b show the formation
of adduct 7, which was observed during the whole course of
the reaction as a small signal *d: 19.59 ppm). In mechanism
a, 7 decomposes to the a-chloro carboxylic acid 8 and
dimethyl phosphate 9 immediately. However, before 9
was perceived, a signal with a 31P chemical shift of
25.75 ppm appeared at the expense of the signal of 2.
According to the literature,20 the 31P chemical shift of
dimethyl acetylphosphate and dimethyl propionylphosphate
is 25.90 and 25.70 ppm, respectively. Consequently, the
Table 1. Yields of a-chloro carboxylic acids 3 and a,a0-dichloro dicar-
boxylic acids 15
Chlorinated carboxylic acid
Yield *%)
2-Chloro valeric acid
3a *nˆ1)
85
55
65
78
75
28
67
54
69
79
2-Chloro decanoic acid
2-Chloro tetradecanoic acid
2-Chloro hexadecanoic acid
2-Chloro octadecanoic acid
2,4-Dichloro glutaric acid
2,5-Dichloro adipic acid
2,7-Dichloro suberic acid
2,8-Dichloro azelaoic acid
2,11-Dichloro dodecanoic-
1,12-diacid
3b *nˆ6)
3c *nˆ10)
3d *nˆ12)
3e *nˆ14)
15a *nˆ1)
15b *nˆ2)
15c *nˆ4)
15d *nˆ5)
15e *nˆ8)

C. V. Stevens, B. Vanderhoydonck / Tetrahedron 57 .2001) 4793±4800
4795
Scheme 4.
observed signal *d: 25.75 ppm) was attributed to dimethyl
a-chloro acylphosphate 10. Essentially, 10 is formed by a
Baeyer±Villiger oxidation of a-chloro acylphosphonate 2.
In accordance with mechanism b, this intermediate should
be hydrolysed yielding 3 and 11. Indeed, the signal of 10
slowly disappeared in favour of the signal of 11 *d:
2.39 ppm). In addition, the same results were obtained
repeating this procedure with an organic peroxide such as
tert-butyl hydroperoxide in an organic solvent leading to the
corresponding a-chloro tert-butyl ester 16c *Table 2).
concentrated hydrogen chloride. The pure a,a0-dichloro
dicarboxylic acids 15 were isolated after crystallization
from the reaction mixture.
The yield of 15a and 15b are in the same order of magnitude
of those reported in the literature.13±15 The higher dicar-
boxylic acids 15c, 15d and 15e are obtained in moderate
to good yield under mild conditions. Except for compound
15c, which was prepared from the corresponding acid, all
a,a0-dichloro dicarboxylic acids 15 were prepared starting
from the corresponding acid chloride 12.
As reported earlier,18 the procedure leads to the formation of
a-chloro carboxylic acids 3 under mild conditions in good
to very good yields *Table 1). Therefore, the procedure was
evaluated to synthesize a,a0-dichloro dicarboxylic acids. In
accordance with the original procedure, the scope of the
reaction was broadened as shown in Scheme 4. These new
results of the one-pot procedure are also listed in Table 1.
Acylphosphonates are not only very sensitive to hydroly-
sis,21 the phosphorus±carbon *P±C) bond is also easily
cleaved by a multitude of nucleophiles such as amines,22
alcohols23 and thiols24 with the expulsion of phosphite.
Consequently, the procedure was evaluated to synthesize
a-chloro esters 16 and a,a0-dichloro diesters 17 by treat-
ment of the corresponding chlorinated acylphosphonates 2
and 14, respectively with ethanol *Scheme 5). The results
are listed in Table 2.
Because of the limited solubility of a,a0-dichloro dicar-
boxylic acids 15 in dichloromethane, the cleavage of 14
was performed in diethyl ether. During the work up of 14
only 2.6 equiv. of hydrogen peroxide and 2.6 equiv. of
sodium bicarbonate were used. The dicarboxylic acids 15
were isolated after acidi®cation of the reaction mixture with
The synthesis of the a-chloro esters 16 was successful. After
an extraction of the crude reaction mixture, 16a and 16b
were obtained as yellow oils with yields over 90%. The pure
Scheme 5.

4796
C. V. Stevens, B. Vanderhoydonck / Tetrahedron 57 .2001) 4793±4800
Table 2. Yields of ethyl a-chloro esters 16, diethyl a,a0-dichloro diesters 17, N-alkyl a-chloro amides 18 and N,N0-diisopropyl a,a0-dichloro diamides 19
Chlorinated ester
Yield *%)
Ethyl 2-chloro decanoate
16a *nˆ6)
16b *nˆ10)
16c *nˆ6)
17a *nˆ1)
17b *nˆ2)
17c *nˆ8)
78
89
55
Ethyl 2-chloro tetradecanoate
tert-Butyl 2-chloro decanoate
Diethyl 2,4-dichloro glutaroate
Diethyl 2,5-dichloro adipoate
Diethyl 2,11-dichloro dodecan-1,12-dioate
a
/
a
/
53
Chlorinated amide
N-Isopropyl 2-chloro decanoylamide
18a *nˆ6)
18b *nˆ10)
18c *nˆ14)
18d *nˆ6)
19a *nˆ1)
19b *nˆ2)
19c *nˆ8)
72
72
74
96 *26)b
4
3
18
N-Isopropyl 2-chloro tetradecanoylamide
N-Isopropyl 2-chloro octadecanoylamide
N-[*S)-1-Phenylethyl] 2-chloro decanoylamide
N,N0-Diisopropyl 2,4-dichloro glutarylamide
N,N0-Diisopropyl 2,5-dichloro adipoylamide
N,N0-Diisopropyl 2,11-dichloro dodecanoyl-1,12-diamide
a
The crude reaction product was a complex mixture from which the chlorinated ester could not be isolated.
The crude mixture was puri®ed by crystallization and this yield is given between brackets.
b
a-chloro esters 16 were isolated by means of ¯ash chroma-
tography using petroleum ether/ethyl acetate as eluent
*Table 2). On the other hand, the preparation of a,a0-
dichloro diesters 17 was less successful. Both ester 17a
and 17b could not be isolated from the complex reaction
mixtures although small amounts were formed. The chlori-
nated ester 17c, however, was formed with a yield of 70%
and could be isolated with a moderate yield after ¯ash
chromatography.
aspects can be deduced from the reaction of a chlorinated
acylphosphonate 2 with a chiral amine, e.g. *S)-1-phenyl-
ethyl amine. Using this chiral amine, a diastereomeric
mixture of amide 18d *50/50) was formed and could be
separated by ¯ash chromatography into the two diastereo-
isomers. The two diastereoisomers revealed a different 13C
NMR value for the CHCl carbon with a difference of
0.12 ppm which was also visible in the crude spectrum of
the diastereomeric mixture. Therefore, it can be concluded
that the diastereoisomers with the chiral centers close to
each other, can be differentiated by the carbon NMR values
of the CHCl carbon.
Analogous to the synthesis of the chlorinated esters, iso-
propyl amine was evaluated as a nucleophile to synthesize
the corresponding chlorinated isopropyl amides *Scheme 6).
In the case of the synthesis of dichloro glutaric acid 15a, the
detection of single peaks in the carbon NMR thus reveals the
synthesis of one diastereomeric pair of acids. Taking into
account the steric interactions, it can be deduced that the
trans enantiomers are formed. However, for higher homo-
logues the steric interaction during the chlorination is negli-
gible which results in mixtures of cis and trans isomers,
which can not be differentiated through the carbon NMR-
values because of the diminished interaction between the
two chiral centers. Therefore, it can be concluded that
during the chlorination, no stereoselectivity is determined
except for the synthesis of short chain difunctionalised
derivatives *low yield) where the trans isomers are
favoured.
Isopropyl amine, as representative for the group of the
amines, appeared to be an ef®cient nucleophile for the
synthesis of a-chlorinated amides 18. The amides 18 were
isolated as yellow solids and puri®ed by crystallization
yielding the pure amides as a white powder. Comparable
to the preparation of the diesters 17a and 17b, the synthesis
of the a,a0-dichloro diamides 19a and 19b was rather
unsuccessful and only very poor yields of pure product
were obtained. Asmall amount of pure amide 19c was
isolated, but the residue still contained approximately 25%
of the product.
Concerning the stereochemistry of the reaction, some
Scheme 6.

C. V. Stevens, B. Vanderhoydonck / Tetrahedron 57 .2001) 4793±4800
4797
In general, this paper describes a straightforward and high
yielding one-pot procedure for the synthesis of a-chloro
acids and a,a0-dichloro diacids and their corresponding
esters and amides. The procedure, however, is not applic-
able to the synthesis of the lower *,C7) a,a0-dichlorinated
diesters and diamides probably due to intramolecular
reactions.
3.4. Procedure for the synthesis of suberoyl chloride 12c
In a round bottom ¯ask of 50 ml, 15 mmol of suberic acid
was dissolved in 20 ml of dichloromethane and was treated
with 39 mmol of thionyl chloride in the presence of
0.8 mmol of N,N-dimethyl formamide *DMF) as a catalyst.
Under a nitrogen atmosphere, the reaction mixture was
re¯uxed for two hours. The dichloromethane was evapo-
rated and the synthesis of the corresponding acylphos-
phonate was started.
3. Experimental
3.1. General
3.4.1. 2,4-Dichloro glutaric acid -15a) as yellowish solid.
1H NMR *270 MHz, *CD3)2vO) d: 2.64 *2H, dd, Jˆ7.9 Hz,
Jˆ6.3 Hz, CH2); 4.67 *2H, dd, Jˆ7.9 Hz, Jˆ6.3 Hz, 2£
CHCl). 13C NMR *68 MHz, CD3OD) d: 39.96 *CH2);
55.02 *2£CHCl); 170.53 *2£CvO). MS: m/z *%): 200/02/
04 *M1, 0.2); 182 *26); 154 *30); 119 *26); 107 *29); 96
*53); 94 *100); 76 *52); 75 *44); 63 *27); 55 *53); 49 *29); 45
*88); 41 *43). IR *cm21) nmax: 1753 *CvO); 1727 *CvO);
1203 *C±O); 1235 *C±O); 3406 *O±H). Mpˆ148±1508C.
Calcd for C5H6Cl2O4: C 29.88, H 3.01. Found: C 30.04, H
2.98.
1H NMR spectra and 13C NMR spectra were recorded at 270
and 68 MHz, respectively. The 31P NMR spectra were
recorded at 109 MHz *JEOL EX 270). CDCl3, CD3OD or
acetone-d6 was used as solvent. Mass spectra were obtained
on a Varian MAT 112 mass spectrometer *70 eV). IR spec-
tra were recorded with a Fourier Transform spectrometer
*Perkin±Elmer, Spectrum One). Diethyl ether was distilled
from sodium/benzophenone ketyl and dichloromethane was
distilled from calcium hydride.
3.4.2. 2,5-Dichloro adipic acid -15b) as yellowish solid. 1H
NMR *270 MHz, CD3OD) d: 2.03 *2H, m, CH2); 2.22 *2H,
m CH2); 4.44 *2H, m, 2£CHCl). 13C NMR *68 MHz,
*CD3)2vO) d: 32.17 *2£CH2); 57.61 *2£CHCl); 170.40
*2£CvO). MS: m/z *%): 214/16/18 *M1, 0.7); 163 *35);
161 *95); 133 *53); 125 *47); 107 *63); 97 *60); 94 *31);
89 *26); 73 *49); 62 *86); 53 *89); 45 *100); 41 *81). IR
*cm21) nmax: 1713 *CvO); 1202 *C±O); 1248 *C±O);
3434 *O±H). Mpˆ135±1378C. Calcd for C6H8Cl2O4: C
33.51, H 3.75. Found: C 33.72, H 3.62.
3.2. Peroxy acid test
In a round bottom ¯ask of 250 ml, 1.5 g of sodium iodide
was dissolved in 50 ml of water, 5 ml of glacial acetic acid
and 5 ml of chloroform. The assumed a,a0-dichloro dicar-
boxylic acid 5e was added and the mixture was stirred. No
colouring due to the formation of iodine was observed.
Consequently, 5e was not a peroxy acid and the procedure
gives rise to the formation of carboxylic acids 3 and 5. To
check the validity of this test, m-chloro perbenzoic acid was
added. After stirring the mixture, an intense colouring was
noticed.
3.4.3. 2,7-Dichloro suberic acid -15c) as yellowish solid.
1H NMR *270 MHz, CD3OD) d: 1.50 *4H, m, 2£CH2); 1.92
*2H, m, CH2CHCl); 2.01 *2H, m, CH2CHCl); 4.35 *2H,
dd, Jˆ7.3 Hz, Jˆ6.3 Hz, 2£CHCl). 13C NMR *68 MHz,
CD3OD) d: 26.38 *2£CH2CH2CHCl); 35.81 *2£CH2CHCl);
58.60 *2£CHCl); 172.88 *2£CvO). MS: m/z *%): 242/44/
46 *M1, 0.4); 151 *17); 149 *55); 131 *25); 113 *45); 96
*39); 94 *100); 81 *23); 79 *25); 67 *34); 55 *64); 45 *54); 41
*81). IR *cm21) nmax: 1712 *CvO); 1228 *C±O). Mpˆ134±
1398C. Calcd for C8H12Cl2O4: C 39.53, H 4.98. Found: C
39.67, H 4.79.
3.3. General procedure for the synthesis of a,a0-dichloro
dicarboxylic acids 15
In a round bottom ¯ask of 50 ml, 32.3 mmol of trimethyl
phosphite was added to 15 mmol of diacid dichloride 12
under a nitrogen atmosphere at 08C. After stirring the reac-
tion mixture for four hours at room temperature, the excess
of trimethyl phosphite and the remainder of methyl chloride
was evaporated in vacuo. The ¯ask was covered with alumi-
nium foil and 39 mmol of sulfuryl chloride was added by
syringe at 08C. The reaction mixture was stirred for 14 h at
room temperature. The chlorination was stopped by adding
5 ml of dry dichloromethane and leading nitrogen gas
through the solution expelling the excess of sulfuryl
chloride and the remaining hydrogen chloride and sulfur
dioxide. The solution was then added to a mixture of
39 mmol of hydrogen peroxide *35% in water), 39 mmol
of sodium bicarbonate and 10 ml of diethyl ether in a
round bottom ¯ask of 50 ml at 08C. After stirring the reac-
tion mixture for 16 h at room temperature, the mixture was
poured in 20 ml of 0.1 M of hydrogen chloride and was
extracted with 20 ml of diethyl ether. The organic layer
was dried over magnesium sulfate, ®ltered and the diethyl
ether was evaporated. Puri®cation of the reaction mixture
was performed by crystallization in dichloromethane and
ethyl acetate yielding the pure a,a0-dichloro dicarboxylic
acid 15 *yield: 28±79%).
3.4.4. 2,8-Dichloro azelaoic acid -15d) as yellowish solid.
1H NMR *270 MHz, CDCl3) d: 1.45 *6H, m, 3£CH2); 1.89
*2H, m, CH2CHCl); 1.98 *2H, m, CH2CHCl); 4.35 *2H, dd,
Jˆ7.3 Hz, Jˆ6.3 Hz, 2£CHCl). 13C NMR *68 MHz,
CDCl3) d: 26.65 *CH2); 29.11 *2£CH2); 35.70 *2£
CH2CHCl); 58.09 *2£CHCl); 171.71 *2£CvO). MS: m/z
*%): no M1, 164 *16); 144 *15); 110 *47); 109 *53); 87 *27);
74 *25); 59 *27); 57 *100); 55 *28); 43 *37); 41 *44). IR
*cm21) nmax: 1734 *CvO); 1210 *C±O); 1306 *C±O).
Mpˆ104±1078C. Calcd for C9H14Cl2O4: C 42.04, H 5.49.
Found: C 42.14, H 5.36.
3.4.5. 2,11-Dichloro dodecanoic-1,12-diacid -15e) as
yellowish solid. 1H NMR *270 MHz, CD3OD) d: 1.33
*8H, s, 4£CH2); 1.43 *4H, m, 2£CH2); 1.92 *4H, m, 2£
CH2CHCl); 4.33 *2H, dd, Jˆ7.6 Hz, Jˆ5.9 Hz, 2£CHCl).
13C NMR *68 MHz, CD3OD) d: 27.29 *2£CH2); 30.20 *2£

4798
C. V. Stevens, B. Vanderhoydonck / Tetrahedron 57 .2001) 4793±4800
CH2); 30.58 *2£CH2); 36.39 *2£CH2CHCl); 59.12 *2£
CHCl); 173.37 *2£CvO). MS: m/z *%): 298/300/02 *0.4);
132 *28); 118 *48); 94 *67); 81 *35); 73 *40); 69 *45); 67
3.6. Procedure for the synthesis of tert-butyl 2-chloro
decanoate 16c
*36); 57 *32); 55 *100); 45 *34); 43 *34); 41 *97). IR *cm21
)
Except for the work up of the a-chloro acylphosphonate 2a,
the procedure is analogous to the synthesis of the a-chlori-
nated esters 16. The a-chloro acylphosphonate 2a was
treated with 10 mmol of pyridine and 10 mmol of tert-
butyl hydroperoxide *3 M in iso-octane) and the reaction
mixture was stirred for 96 h under nitrogen atmosphere at
room temperature. The reaction mixture was poured in
20 ml of 0.1 M of hydrogen chloride and was extracted
with 20 ml of dichloromethane. The organic layer was
dried over magnesium sulfate, ®ltered and the dichloro-
methane was evaporated. The chlorinated tert-butyl ester
was isolated by ¯ash chromatography using petroleum
ether and ethyl acetate as eluent *yield: 55%).
nmax: 1711 *CvO); 1215 *C±O); 1239 *C±O). Mpˆ99±
1028C. Calcd for C12H20Cl2O4: C 48.17, H 6.74. Found: C
48.09, H 6.82.
3.5. General procedure for the synthesis of a-chloro
esters 16
In a round bottom ¯ask of 50 ml, 5.8 mmol of trimethyl
phosphite was added to 5 mmol of acid chloride under a
nitrogen atmosphere at 08C. After stirring the reaction
mixture for four hours at room temperature, the excess of
trimethyl phosphite and the remainder of methyl chloride
was evaporated in vacuo. The ¯ask was covered with alu-
minium foil and 6.5 mmol of sulfuryl chloride was added by
syringe at 08C. The reaction mixture was stirred for 14 h at
room temperature. The reaction was quenched by addition
of 5 ml of dry dichloromethane and nitrogen gas was led
through the solution in order to remove the excess of sul-
furyl chloride and the remaining hydrogen chloride and
sulfur dioxide. The solution was added to 6.5 mmol of abso-
lute ethanol dissolved in 10 ml of dry dichloromethane at
08C. After stirring the reaction mixture for 16 h under a
nitrogen atmosphere at room temperature, the mixture was
poured in 20 ml of 0.1 M of hydrogen chloride and was
extracted with 20 ml of dichloromethane. The organic
layer was dried over magnesium sulfate, ®ltered and the
dichloromethane was evaporated. Puri®cation of the
reaction mixture was performed by ¯ash chromatography
using petroleum ether and ethyl acetate as the eluent
*yield: 78±89%).
3.6.1. tert-Butyl 2-chloro decanoate -16c) as yellow oil. 1H
NMR *270 MHz, CDCl3) d: 0.88 *3H, t, Jˆ6.4 Hz, CH3);
1.27 *12H, s, 6£CH2); 1.35 *9H, s, C*CH3)3); 2.00 *2H, m,
CH2CHCl); 4.27 *1H, m, CHCl). 13C NMR *68 MHz,
CDCl3) d: 13.95 *CH3); 22.50 *CH2); 25.77 *C*CH3));
25.86 *2£C*CH3)); 28.66 *CH2); 28.97 *CH2); 29.02
*CH2); 29.11 *CH2); 31.65 *CH2); 34.77 *CH2CHCl);
54.38 *CHCl); 84.46 *C*CH3)3); 167.21 *CvO). MS: m/z
*%): no M1; 160 *3); 142 *4); 108 *6); 88 *12); 86 *68); 84
*100); 57 *14); 49 *14); 47 *18). IR *cm21) nmax: 1046
*C±O); 1189 *C±O); 1786 *CvO). Flash chromatography:
*PE/EtOAc:10/90): Rfˆ0.7. Calcd for C14H27ClO2: C 63.98,
H 10.35. Found: C 63.73, H 11.60.
3.7. Procedure for the synthesis of diethyl 2,11-dichloro
dodecan-1,12-dioate 17c
The procedure is analogous to the synthesis of the a-chlori-
nated esters 16. The following amounts of reagents were
used: 5 mmol of dodecanoyl dichloride 12e, 10.8 mmol of
trimethyl phosphite and 13 mmol of sulfuryl chloride. The
a,a0-dichloro bisacylphosphonate 14e was added to a round
bottom ¯ask of 50 ml containing 13 mmol of absolute
ethanol dissolved in 10 ml of dry dichloromethane at 08C.
The reaction mixture was stirred for four hours under a
nitrogen atmosphere at room temperature. The mixture
was poured in 20 ml of 0.1 M of hydrogen chloride and
was extracted with 20 ml of dichloromethane. The organic
layer was dried over magnesium sulfate, ®ltered and the
dichloromethane was evaporated. The chlorinated ester
17c was isolated by ¯ash chromatography using petroleum
ether and ethyl acetate as eluent *yield: 53%).
1
3.5.1. Ethyl 2-chloro decanoate -16a) as yellow oil. H
NMR *270 MHz, CDCl3) d: 0.88 *3H, t, Jˆ6.6 Hz, CH3);
1.31 *13H, m, CH3CH2O, 5£CH2); 1.40 *2H, m,
CH2CH2CHCl), 1.97 *2H, m, CH2CHCl); 4.24 *3H, m,
CH2O, CHCl). 13C NMR *68 MHz, CDCl3) d: 13.86
*CH3); 13.89 *CH3); 22.48 *CH2); 25.81 *CH2); 28.72
*CH2); 28.99 *CH2); 29.13 *CH2); 31.65 *CH2); 34.74
*CH2CHCl); 57.23 *CH2O); 61.67 *CHCl). 169.60
*CvO). MS: m/z *%): 234 *M1, 2); 177 *17); 124 *32);
122 *100); 94 *20); 85 *51); 83 *82); 69 *19); 57 *19);
55 *21); 43 *23). IR *cm21) nmax: 1747 *CvO). Flash
chromatography: *PE/EtOAc:20/80): Rfˆ0.7. Calcd for
C12H23ClO2: C 61.39, H 9.87. Found: C 61.33, H 9.78.
3.5.2. Ethyl 2-chloro tetradecanoate -16b) as yellow oil.
1H NMR *270 MHz, CDCl3) d: 0.88 *3H, t, Jˆ6.6 Hz,
CH3); 1.26 *23H, m, CH3CH2O, 10£CH2); 1.95 *2H, m,
CH2CHCl); 4.24 *3H, m, CHCl, CH2O). 13C NMR
*68 MHz, CDCl3) d: 13.91 *CH3); 13.98 *CH3); 22.59
*CH2); 25.86 *CH2); 28.77 *CH2); 29.26 *2£CH2); 29.38
*CH2); 29.54 *3£CH2); 31.83 *CH2); 34.79 *CH2CHCl);
57.27 *CH2O); 61.73 *CHCl); 169.65 *CvO). MS: m/z
*%): 290/92 *M1, 0.8); 124 *9); 122 *28); 87 *12); 85
3.7.1. Diethyl 2,11-dichloro dodecan-1,12-dioate -17c) as
yellow oil. H NMR *270 MHz, CDCl3) d: 1.31 *14H, m,
1
4£CH2, 2£CH3); 1.40 *4H, m, 2£CH2CH2CHCl); 1.97 *4H,
m, 2£CH2CHCl); 4.24 *6H, m, 2£CH2O, 2£CHCl). 13C
NMR *68 MHz, CDCl3) d: 13.80 *2£CH3); 25.64 *2£
CH2); 28.52 *2£CH2); 28.88 *2£CH2); 34.59 *2£
CH2CHCl); 57.16 *2£CH2O); 61.65 *2£CHCl); 169.52
*2£CvO). MS: m/z *%): no M1; 140 *16); 125 *17); 111
*14); 99 *10); 85 *62); 83 *100); 59 *16); 49 *11); 48 *17);
47 *30); 45 *15). IR *cm21) nmax: 1747 *CvO). Flash
chromatography: *PE/EtOAc:40/60): Rfˆ0.6. Calcd for
C16H28Cl2O4: C 54.09, H 7.94. Found: C 53.91, H 8.00.
*66); 83 *100); 57 *7); 55 *7); 47 *16); 41 *6). IR *cm21
max: 1747 *CvO). Flash chromatography: *PE/EtOAc:30/
)
n
70): Rfˆ0.6. Calcd for C16H31ClO2: C 66.07, H 10.74.
Found: C 65.97, H 10.61.

C. V. Stevens, B. Vanderhoydonck / Tetrahedron 57 .2001) 4793±4800
4799
3.8. General procedure for the synthesis of a-chloro
amides 18
*5£CH2); 31.93 *CH2); 35.62 *CH2CHCl); 41.90 *NCH);
61.58 *CHCl); 168.10 *CvO). MS: m/z *%): 359/61 *M1;
12); 346 *7); 326 *12); 191 *7); 149 *7); 138 *43); 136 *100);
87 *41); 55 *10); 43 *29). IR *cm21) nmax: 1651 *CvO);
3295 *NH); 1553 *NH). Mpˆ76±828C. Calcd for
C21H42ClNO: C 70.06, H 11.76. Found: C 70.18, H 11.65.
The procedure is analogous to the synthesis of the a-chlori-
nated esters 16. 5 mmol of acid chloride and 5.8 mmol of
trimethyl phosphite were used for the synthesis of acyl-
phosphonate 1 and the chlorination was performed with
6.5 mmol of sulfuryl chloride. The chlorinated acylphos-
phonate 2 was added to a round bottom ¯ask of 50 ml
containing 6.5 mmol of isopropyl amine *or *S)-1-phenyl-
ethyl amine) dissolved in 10 ml of dry dichloromethane at
08C. The reaction mixture was stirred for four hours under a
nitrogen atmosphere at room temperature. The reaction
mixture was poured in 20 ml of 0.1 M of hydrogen chloride
and was extracted with 20 ml of dichloromethane. After
drying the organic layer over magnesium sulfate and ®l-
tration, the dichloromethane was evaporated and the pure
a-chloro amide 18 was isolated by crystallization using
dichloromethane and petroleum ether *yield: 72±74%).
3.8.4. N-[-S)-1-Phenylethyl] 2-chloro decanoylamide
-18d). Mixture of diastereoisomers. *a) White solid. H
1
NMR *270 MHz, CDCl3) d: 0.88 *3H, t, Jˆ6.6 Hz, CH3);
1.28 *10H, s, 5£CH2); 1.47 *2H, s, CH2); 1.52 *3H, d, Jˆ
6.9 Hz, NCHCH3); 1.94 *1H, m, CH2CHCl); 2.11 *1H, m,
CH2CHCl); 4.33 *1H, dd, Jˆ8.3 Hz, Jˆ4.0 Hz, CHCl); 5.10
*1H, m, NCH); 6.81 *1H, d, Jˆ7.3 Hz, NH); 7.33 *5H, m,
C6H5). 13C NMR *68 MHz, CDCl3) d: 14.07 *CH3); 21.71
*CH3); 22.61 *CH2); 25.77 *CH2); 28.82 *CH2); 29.15 *CH2);
29.31 *CH2); 31.77 *CH2); 35.54 *CH2CHCl); 49.20 *NCH);
61.46 *CHCl); 126.04 *2£CH); 127.51 *CH); 128.73 *2£
CH); 142.48 *Cquat); 168.10 *CvO). MS: m/z *%): 309/11
*M1, 1.2); 212 *18); 157 *32); 150 *23); 136 *27); 125 *42);
122 *100); 121 *30); 119 *65); 108 *31); 94 *55); 85 *44); 83
*61); 76 *13); 55 *28); 43 *26). IR *cm21) nmax: 1650
*CvO); 3288 *NH); 1545 *NH). Flash chromatography:
*PE/EtOAc: 95/5): Rfˆ0.20. Mpˆ75±778C. Calcd for
C19H28ClNO: C 69.77, H 9.11. Found: C 69.54, H 9.01.
3.8.1. N-Isopropyl 2-chloro decanoylamide -18a) as
yellowish solid. H NMR *270 MHz, CDCl3) d: 0.88 *3H,
1
t, Jˆ6.6 Hz, CH3); 1.18 *3H, d, Jˆ6.3 Hz, CH*CH3)); 1.19
*3H, d, Jˆ6.3 Hz, CH*CH3)); 1.27 *10H, s, 5£CH2); 1.45
*2H, s, CH2); 1.92 *1H, m, CH2CHCl); 2.07 *1H, m,
CH2CHCl); 4.07 *1H, m, CH*CH3)2); 4.31 *1H, dd, Jˆ
7.9 Hz, Jˆ4.0 Hz, CHCl); 6.46 *1H, s, NH). 13C NMR
*68 MHz, CDCl3) d: 14.34 *CH3); 22.70 *CH3); 22.77
*CH3); 22.90 *CH3); 26.06 *CH2); 29.13 *CH2); 29.42
*CH2); 29.60 *CH2); 32.06 *CH2); 35.83 *CH2CHCl);
42.14 *NCH); 61.69 *CHCl); 168.39 *CvO). MS: m/z
*%): 247/49 *M1, 5); 232 *7); 212 *13); 137 *34); 135
*100); 100 *15); 86 *60); 83 *16); 55 *11); 44 *30); 43
*46). IR *cm21) nmax: 1650 *CvO); 3295 *NH); 1551
*NH). Mpˆ 57±598C. Calcd for C13H26ClNO: C 63.01, H
10.58. Found: C 63.22, H 10.72.
*b) White solid. 1H NMR *270 MHz, CDCl3) d: 0.87 *3H, t,
Jˆ6.6 Hz, CH3); 1.24 *10H, s, 5£CH2); 1.41 *2H, s, CH2);
1.52 *3H, d, Jˆ6.9 Hz, NCHCH3); 1.89 *1H, m, CH2CHCl);
2.06 *1H, m, CH2CHCl); 4.36 *1H, dd, Jˆ8.3 Hz, Jˆ4.0 Hz,
CHCl); 5.10 *1H, m, NCH); 6.82 *1H, d, Jˆ7.3 Hz, NH);
7.32 *5H, m, C6H5). 13C NMR *68 MHz, CDCl3) d: 14.09
*CH3); 21.74 *CH3); 22.64 *CH2); 25.77 *CH2); 28.82 *CH2);
29.13 *CH2); 29.33 *CH2); 31.82 *CH2); 35.61 *CH2CHCl);
49.22 *NCH); 61.58 *CHCl); 126.02 *2£CH); 127.51 *CH);
128.75 *2£CH); 142.67 *Cquat); 168.15 *CvO). MS: m/z
*%): 309/11 *M1, 1.2); 212 *18); 157 *32); 150 *23); 136
*27); 125 *42); 122 *100); 121 *30); 119 *65); 108 *31); 94
3.8.2. N-Isopropyl 2-chloro tetradecanoylamide -18b) as
yellowish solid. 1H NMR *270 MHz, CDCl3) d: 0.88 *3H, t,
Jˆ6.6 Hz, CH3); 1.18 *3H, d, Jˆ6.6 Hz, CH*CH3)); 1.19
*3H, d, Jˆ6.6 Hz, CH*CH3)); 1.25 *18H, s, 9£CH2); 1.45
*2H, s, CH2); 1.91 *1H, m, CH2CHCl); 2.08 *1H, m,
CH2CHCl); 4.07 *1H, m, CH*CH3)2); 4.31 *1H, dd, Jˆ
8.3 Hz, Jˆ4.0 Hz, CHCl); 6.41 *1H, s, NH). 13C NMR
*68 MHz, CDCl3) d: 14.07 *CH3); 22.43 *CH3); 22.52
*CH3); 22.64 *CH2); 25.75 *CH2); 28.81 *CH2); 29.33
*CH2); 29.47 *CH2); 29.60 *4£CH2); 31.88 *CH2); 35.56
*CH2CHCl); 41.85 *NCH); 61.57 *CHCl); 168.05 *CvO).
MS: m/z *%): 303/05 *M1, 10); 269 *24); 227 *6); 191 *6);
138 *28); 136 *82); 86 *64); 84 *100); 47 *17); 44 *14); 43
*25). IR *cm21) nmax: 1650 *CvO); 3295 *NH); 1551 *NH).
Mpˆ76±788C. Calcd for C17H34ClNO: C 67.18, H 11.28.
Found: C 67.30, H 11.10.
*55); 85 *44); 83 *61); 76*13); 55 *28); 43 *26). IR *cm21
max: 1656 *CvO); 3292 *NH); 1557 *NH). Flash
)
n
chromatography *PE/EtOAc: 95/5): Rfˆ0.25. Mpˆ75±
778C. Calcd for C19H28ClNO: C 69.77, H 9.11. Found: C
69.54, H 9.01.
3.9. General procedure for the synthesis of a,a-dichloro
diamides 19
The procedure is analogous to the synthesis of the a-chlori-
nated amides 18. The following amounts of reagents were
used: 5 mmol of diacid dichloride, 10.8 mmol of trimethyl
phosphite and 13 mmol of sulfuryl chloride. The a,a0-
dichloro bisacylphosphonate 14 was added to a round
bottom ¯ask of 50 ml containing 13 mmol of isopropyl
amine dissolved in 10 ml of dry dichloromethane at 08C.
The reaction was stirred for four hours under a nitrogen
atmosphere at room temperature. The a,a0-dichloro amides
19a and 19b were isolated by dissolving the resulting brown
oil in a small amount of methanol and placing this solution
for 24 h at 2188C *yield: 3±4%). The chlorinated amide 19c
was isolated by extraction of the reaction mixture with
20 ml of dichloromethane and by crystallization using
ethyl acetate and chloroform *yield: 18%).
3.8.3. N-Isopropyl 2-chloro octadecanoylamide -18c) as
yellowish solid. 1H NMR *270 MHz, CDCl3) d: 0.88 *3H, t,
Jˆ6.6 Hz, CH3); 1.18 *3H, d, Jˆ6.6 Hz, CH*CH3)); 1.19
*3H, d, Jˆ6.6 Hz, CH*CH3)); 1.25 *26H, s, 13£CH2); 1.45
*2H, s, CH2); 1.90 *1H, m, CH2); 2.10 *1H, m, CH2); 4.07
*1H, m, CH*CH3)2); 4.31 *1H, dd, Jˆ8.3 Hz, Jˆ4.0 Hz,
CHCl); 6.39 *1H, s, NH). 13C NMR *68 MHz, CDCl3) d:
14.14 *CH3); 22.46 *CH3); 22.57 *CH3); 22.71 *CH2); 25.80
*CH2); 28.88 *CH2); 29.40 *3£CH2); 29.52 *2£CH2); 29.70

4800
C. V. Stevens, B. Vanderhoydonck / Tetrahedron 57 .2001) 4793±4800
3.9.1. N,N0-Diisopropyl 2,4-dichloro glutarylamide -19a)
as yellowish solid. H NMR *270 MHz, CDCl3) d: 1.18
Soc. Anon.). US Patent Application, 8 Feb., 1961, 16pp.
*c) Sagal, Jr., J.; Allen, F. D. *Kodac Soc. Anon.). Chem.
Abstr. 1962, 57, 16044e.
1
*6H, d, Jˆ6.3 Hz, 2£CH3); 1.20 *6H, d, Jˆ4.6 Hz, 2£
CH3); 2.64 *2H, m, CH2); 4.07 *2H, m, 2£NCH); 4.54
*2H, m, 2£CHCl); 6.45 *2H, s, 2£NH). 13C NMR
*68 MHz, CDCl3) d: 22.41 *4£CH3); 41.33 *CH2); 42.16
*2£NCH); 57.70 *2£CHCl); 166.77 *2£CvO). MS: m/z
*%): 282/84/86 *M1, 10); 227 *41); 225 *67); 191 *34);
182 *22); 160 *29); 148 *37); 137 *32); 135 *100); 118
*36); 44 *34); 43 *49). IR *cm21) nmax: 1651 *CvO); 3250
*NH); 1562 *NH). Mpˆ177±1818C. Calcd for
C11H20Cl2N2O2: C 46.65, H 7.12. Found: C 46.72, H 7.14.
5. Harpp, D. N.; Bao, L. Q.; Black, C. J.; Gleason, J. G.; Smith,
R. A. J. Org. Chem. 1975, 40, 3420±3427.
6. Crawford, R. J. J. Org. Chem. 1983, 48, 1364±1366.
7. Ogata, Y.; Harada, T.; Matsuyama, K.; Ikejiri, T. J. Org.
Chem. 1975, 40, 2960±2962.
8. *a) Ogata, Y.; Sugimoto, T.; Inaishi, M. Bull. Chem. Soc. Jpn.
1979, 52, 255±256. *b) Ogata, Y.; Sugimoto, T.; Inaishi, M.
Chem. Abstr. 1979, 90, 203444d.
9. *a) Gibson, M. S.; Howie, J. K. Eur. Patent Application EP
87,835 *Cl. C07C51/363), 07 Sept., 1983. *b) Gibson, M. S.;
Howie, J. K. US Patent Application 353,285, 01 Mar., 1982,
13pp. *c) Gibson, M. S.; Howie, J. K. Chem. Abstr. 1984, 100,
5863b.
3.9.2. N,N0-Diisopropyl 2,5-dichloro adipoylamide -19b)
1
as yellowish solid. H NMR *270 MHz, CDCl3) d: 1.19
*12H, d, Jˆ6.6 Hz, 4£CH3); 2.11 *2H, m, CH2); 2.31 *2H,
m, CH2); 4.06 *2H, m, 2£NCH); 4.34 *2H, m, 2£CHCl);
6.41 *2H, s, 2£NH). 13C NMR *68 MHz, CDCl3) d: 22.43
*2£CH3); 22.54 *2£CH3); 32.00 *2£CH2); 42.09 *2£NCH);
60.20 *CHCl); 60.29 *CHCl); 167.19 *2£CvO). MS: m/z
*%): 296/98/300 *M1, 20); 198 *31); 165 *40); 163 *43); 149
*31); 114 *42); 113 *33); 96 *54); 69 *57); 67 *34); 57 *31);
55 *57); 52 *35); 44 *100); 43 *80). IR *cm21) nmax: 1652
*CvO); 3287 *NH); 1556 *NH). Mpˆ209±2128C. Calcd
for C12H22Cl2N2O2: C 48.49, H 7.46. Found: C 48.43, H
7.39.
10. *a) Procter and Gamble Co. Jpn. Kokai Tokyo Koho 79 39,013
*Cl. C07C53/32), 24 Mar., 1979. *b) Procter and Gamble Co.
US Patent Application 814,963, 12 July, 1977, 8pp. *c) Procter
and Gamble Co. Chem. Abstr. 1979, 91, 19907b.
11. Rodin, R. L.; Gershon, H. J. Org. Chem. 1973, 38, 3919±
3921.
12. *a) Danechrad, A. O. J. Rech. Center Natt. Rech. Sci. Lab.
Bellevue .Paris) 1963, 63, 255±281. *b) Danechrad, A. O.
Chem. Abstr. 1964, 61, 568h.
13. Treibs, W.; Michaelis, K. Chem. Ber. 1955, 88, 402±407.
14. Buechel, K. H.; Ginsberg, A. E.; Fischer, R. Chem. Ber. 1966,
99, 421±430.
3.9.3. N,N0-Diisopropyl 2,11-dichloro dodecanoyl-1,12-
diamide -19c) as yellowish solid. H NMR *270 MHz,
1
15. Treibs, W.; Walther, H. Chem. Ber. 1955, 88, 396±402.
16. *a) Satoshi, M.; Tadashi, S.; Etsuo, T.; Kenichi, A.; Akihiro, S.
Japan Patent 68 20, 163 *Cl. 16 B 64), 30 Aug., 1968.
*b) Satoshi, M.; Tadashi, S.; Etsuo, T.; Kenichi, A.; Akihiro,
S. Japan Patent Application, 13 Aug., 1966, 2pp. *c) Satoshi,
M.; Tadashi, S.; Etsuo, T.; Kenichi, A.; Akihiro, S. Chem.
Abstr. 1969, 70, 57160b.
CDCl3) d: 1.18 *6H, d, Jˆ6.6 Hz, 2£CH3); 1.19 *6H, d,
Jˆ6.6 Hz, 2£CH3); 1.29 *8H, s, 4£CH2); 1.45 *4H, s, 2£
CH2); 1.91 *2H, m, CH2CHCl); 2.08 *2H, m, CH2CHCl);
4.08 *2H, m, 2£NCH); 4.31 *2H,dd, Jˆ8.3 Hz, Jˆ3.9 Hz,
2£CHCl); 6.41 *2H, d, Jˆ6.6 Hz, 2£NH). 13C NMR
*68 MHz, CDCl3) d: 22.44 *2£CH3); 22.55 *2£CH3);
25.71 *2£CH2); 28.75 *2£CH2); 29.16 *2£CH2); 35.54
*2£CH2CHCl); 41.94 *2£NCH);61.49 *2£CHCl); 168.16
*2£CvO). MS: m/z *%): 380/82/84 *M1, 2); 235 *84);
221 *59); 193 *100); 165 *52); 109 *28); 91 *26); 82 *78);
66 *86); 57 *69); 55 *57); 49 *75); 47 *82); 42 *43); 41 *55).
IR *cm21) nmax: 1652 *CvO); 3288 *NH); 1552 *NH). Mpˆ
118±1218C. Calcd for C18H34Cl2N2O2: C 56.69, H 8.99.
Found: C 56.74, H 7.12.
17. Shakhnazaryan, G. M.; Shakhbatyan, S. L. Arm. Khim. Zh.
1981, 34, 701±702.
18. Stevens, C.; De Buyck, L.; De Kimpe, N. Tetrahedron Lett.
1998, 39, 8739±8742.
19. Furniss, B. S.; Hannaford, A. J.; Smith, P. W. G.; Tatchell,
A . R. InVogel's Textbook of Practical Organic Chemistry, 5,
Longman Scienti®c and Technical: Essex, UK, 1989; pp 1514.
Copublished in the United States with Wiley: New York.
20. Gordon, N. J.; Evans, Jr., S. A. J. Org. Chem. 1993, 58, 4516±
4519.
References
21. Afarinkia, K.; Echenique, J.; Nyburg, S. C. Tetrahedron Lett.
1997, 38, 1663±1666.
1. Hwang, Y. S.; Navvab-Gojrati, H. A.; Mulla, M. S. J. Agric.
Food. Chem. 1978, 26, 1293±1296.
22. Sekine, M.; Satoh, M.; Yamagata, H.; Hata, T. J. Org. Chem.
1980, 45, 4162±4167.
2. Scheffrahn, R. H.; Su, N. Y. J. Econ. Entomol. 1987, 80, 312±
316.
23. Sekine, M.; Kume, A.; Hata, T. Tetrahedron Lett. 1981, 22,
3617±3620.
3. *a) Sollin, I. US Patent 3,353,672, *Cl. 209-166), 21 Nov.,
1967. *b) Sollin, I. US Patent Application, 21 May, 1964,
2pp. *c) Sollin, I. Chem. Abstr. 1968, 68, 61061w.
4. *a) Sagal, Jr., J.; Allen, F. D. *Kodac Soc. Anon.). Belg. Patent
613,565, 28 Feb., 1962. *b) Sagal, Jr., J.; Allen, F. D. *Kodac
24. Breuer, E. Acylphosphonates and their derivatives. In The
Chemistry of Organophosphorus Compounds; Hartley, F. R.,
Ed.; Wiley: New York, 1996; Vol. 4, pp 653±729.